Ide-Cel Generates Durable Responses in Functionally High-Risk Myeloma

OncLive^® originally published this article; this version has been lightly edited.

Idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb/2seventy bio, Inc) induced durable responses and had a favorable risk-benefit profile in patients with functionally high-risk multiple myeloma who relapsed within 18 months of receiving first-line therapy, according to findings from cohort 2B of the phase 2 KarMMa-2 trial (NCT03601078) presented during the the European Hematology Association 2024 Congress.¹

The overall response rate (ORR) in those who had a response but were treated in the frontline setting was 80.6% (95% CI, 62.5%-92.5%) vs 93.5% (95% CI, 78.6%-99.2%) in those with responses to ide-cel. Between both groups, the complete response (CR) rate was 3.2% (95% CI, 0.1%-16.7%) vs 71.0% (95% CI, 52.0%-85.8%).

Minimal residual disease (MRD) was assessed between 3 and 36 months following treatment with ide-cel. At 3 months, 11% of patients were MRD positive, 11% were MRD intermediate, and 79% were MRD negative. Subsequently, at 6 months, MRD rates showed 18% were MRD positive and 82% were MRD negative; at 12 months, 19% vs 81%; at 18 months, 20% vs 80%; at 24 months, 18% vs 82%; and at 36 months, 25% vs 75%.

The rate of ongoing responses at 24 months was 65.3% in patients with a response vs 75.7% in patients with a CR or better. The progression-free survival rate at 12 months was 70.0%; at 24 months, it was 63.3%. The overall survival (OS) rate at 12 months was 89.9% vs 78.9% at 24 months.

The investigators noted that the median PFS was not reached, and at data cutoff, the median OS was not reached.

Xavier Leleu, MD, MSc, PhD | Image Credit: Poitiers University Hospital

“Although a high proportion of patients had high tumor burden and high-risk cytogenetics, response rates were high,” Xavier Leleu, MD, MSc, PhD, head of the Myeloma Clinic at Poitiers University Hospital in Lille France, said during a presentation of the data.

Cohort 2B included 35 patients with an early relapse. Patients needed to have received frontline therapy with a proteasome inhibitor, immunomodulatory drug, and dexamethasone; have measurable disease; and have an Eastern Cooperative Oncology Group performance status of 0 or 1 to be included.

Ide-cel was given at 150 to 450 x 106 CAR-positive T cells. The primary end point was CR rate by investigator assessment per the International Myeloma Working Group criteria. Secondary end points included ORR, time to response, duration of response, PFS, OS, and safety. The exploratory end points were MRD negativity and biomarkers.

At the data cutoff of December 13, 2023, the median follow-up was 30.1 months. During this time, 64.5% of patients were still on study treatment. Reasons for discontinuation included death (22.6%), withdrawal by patient (9.7%), or physician decision (3.2%).

The median patient age was 60 years, with 41.9% of patients being 65 years or older and 29.0% being 70 years or older. The median time to progression during frontline therapy was 7.1 months, and 45.2% of patients had a high tumor burden. Additionally, 38.7% of patients were high risk, and 16.1% were ultra high risk. Extramedullary disease was noted in 12.9% of patients, 67.7% were double-class refractory, 16.1% were triple-class refractory, and 16.1% were triple-class exposed.

As frontline therapy, most patients (38.7%) received bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone plus bortezomib, thalidomide, and dexamethasone; or other (41.9%) treatment. Of note, 87.1% of patients received any type of bridging therapy.

In response to ide-cel, 64.5% of patients had a stringent CR vs 0.0% in patients with a response to frontline treatment, 6.5% vs 3.2% had a CR, 12.9% vs 41.9% had a very good partial response (PR), and 9.7% vs 35.5% had a PR.

Grade 3 or higher adverse effects (AEs) were noted in 93.5% of patients. The most common hematologic AEs were neutropenia (93.5%), anemia (54.8%), thrombocytopenia (35.5%), lymphopenia (45.2%), and leukopenia (38.7%). Of note, 6.5% of patients had arthralgia, 12.9% had metabolism and nutrition disorders, 6.5% had gastrointestinal disorders, and 6.5% had nervous system disorders. Additionally, 19.4% of patients had infections or infestations.

The median time to recovery was 1.5 months (95% CI, 1.3-1.5) for grade 3/4 neutropenia and 2.0 months (95% CI, 1.4-not evaluable) for thrombocytopenia. One patient reported a secondary malignancy of Bowen’s disease.

Cytokine release syndrome (CRS) occurred in 83.9% of patients, although 0.0% had grade 3 or higher events. A total of 94.4% of CRS events were managed with tocilizumab.

The European Organization for Research and Treatment of Cancer core quality of life questionnaire found patient-reported improvement in overall quality of life. There was a clinically meaningful improvement by month 3 in 85% or more of patients.

Ide-cel was approved by the FDA in April for earlier treatment of relapsed/refractory multiple myeloma, among patients who have failed at least 2 prior therapies, based on KarMMa-3 (NCT03651128) phase 3 trial data.^2,3

References

1. Leleu X, Chung, A, Raje N, et al. Idecabtagene vicleucel in patients with clinical high-risk early relapse multiple myeloma without front-line autologous stem cell transplantation: KarMMa-2 cohort 2b. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. S208.

2. Efficacy and safety study of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM) (KarMMa-3). ClinicalTrials.gov. Updated December 15, 2022. Accessed June 28, 2024. https://clinicaltrials.gov/study/NCT03651128

3. Bonavitacola J. Ide-cel receives approval for earlier treatment for relapsed-refractory multiple myeloma. The American Journal of Managed Care^®. April 5, 2004. Accessed June 28, 2024. https://www.ajmc.com/view/ide-cel-receives-approval-for-earlier-treatment-for-relapsed-refractory-multiple-myeloma